Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Projected effectiveness of lung cancer screening and concurrent smoking cessation support in the Netherlands.

Background: The NELSON trial demonstrated a 24% intention-to-screen reduction in lung cancer mortality from regular screening with low-dose computed tomography. Implementation efforts in Europe are ongoing, but still await country-specific and NELSON-adapted estimates of the benefits and harms of screening. Methods: We use the MISCAN-Lung microsimulation model, calibrated to individual-level outcomes from the NELSON trial, to estimate the effectiveness under 100% compliance of biennial lung cancer screening with concomitant smoking cessation support for Dutch cohorts 1942-1961. The model simulates smoking behaviour, lung cancer incidence and the effects of screening and smoking cessation on lung- and other-cause mortality. Findings: We find biennial screening with eligibility criteria equal to those of the 4-IN-THE-LUNG-RUN implementation trial to reduce lung cancer mortality by 16.9% among the eligible population, equivalent to 1076 LC deaths prevented per year in the next two decades. Eligible individuals constitute 21.5% of the cohorts studied, and stand to face 61% of the projected lung cancer mortality burden in the absence of screening. 10.3 life-years are gained per prevented LC death, for 14.9 screens per life year gained. Concomitant smoking cessation interventions may increase the expected gains in life years from screening by up to 20%. Interpretation: Policy makers should imminently consider the implementation of lung cancer screening in Europe, paired with effective smoking cessation interventions. Smoking cessation interventions on their own are not estimated to yield a gain in remaining life expectancy of the magnitude offered by even a single CT screen. Funding: European UnionHorizon 2020 grant 848294: 4-IN-THE-LUNG-RUN.

Medical costs of lung cancer by stage, histology and first-line treatment modality in the Netherlands (2012-2021).

INTRODUCTION: Lung cancer is a leading cause of mortality worldwide, with lung cancer treatment presenting a significant financial burden. The treatment landscape has recently shifted, seeing an increase in targeted- and immunotherapies. Such treatments are expensive, but estimates of the medical costs of the lung cancer treatment pathway largely predate their introduction. METHODS: We link medical expenditures of individuals resident in the Netherlands (n = 19.2 m) for 2013-2021 to tumour-level (n = 137,129, incident 2012-2021) Netherlands Cancer Registry data. We estimate lung cancer-attributable costs by phase of care (initial, continuing and terminal), stratified by cancer stage and histology, and observe trends in medical costs over time. RESULTS: We estimate mean costs over the lung cancer treatment pathway to be €48,443 per patient. Total medical costs are highest in the initial phase, followed by the terminal and continuing phase. Monthly treatment for stage IV lung cancer is significantly more expensive than for early-stage disease (€8293 per month of initial care relative to €3228 for stage IA). Stage IV lung cancer has become significantly more expensive to treat 2018-2021 relative to 2013-2017, with monthly expenditures rising 55 % in initial care and 148 % in continuing care. Population-wide, we find €900.6 million spent on lung cancer care in 2021, €433 million more than in 2016, of which €307.3 million is attributed to per-patient expenditure trends. CONCLUSIONS: Treatment advances are quickly inflating medical costs for late-stage lung cancer. Policy makers should carefully evaluate the cost-effectiveness of novel treatments, and incorporate stage-specific treatment costs in evaluating interventions for early detection.

Screening for liver fibrosis: lessons from colorectal and lung cancer screening.

Many countries have incorporated population screening programmes for cancer, such as colorectal and lung cancer, into their health-care systems. Cirrhosis is more prevalent than colorectal cancer and has a comparable age-standardized mortality rate to lung cancer. Despite this fact, there are no screening programmes in place for early detection of liver fibrosis, the precursor of cirrhosis. In this Perspective, we use insights from colorectal and lung cancer screening to explore the benefits, challenges, implementation strategies and pathways for future liver fibrosis screening initiatives. Several non-invasive methods and referral pathways for early identification of liver fibrosis exist, but in addition to accurate detection, screening programmes must also be cost-effective and demonstrate benefit through a reduction in liver-related mortality. Randomized controlled trials are needed to confirm this. Future randomized screening trials should evaluate not only the screening tests, but also interventions used to halt disease progression in individuals identified through screening.

How will lung cancer screening and lung nodule management change the diagnostic and surgical lung cancer landscape?

INTRODUCTION: Implementation of lung cancer screening, with its subsequent findings, is anticipated to change the current diagnostic and surgical lung cancer landscape. This review aimed to identify and present the most updated expert opinion and discuss relevant evidence regarding the impact of lung cancer screening and lung nodule management on the diagnostic and surgical landscape of lung cancer, as well as summarise points for clinical practice. METHODS: This article is based on relevant lectures and talks delivered during the European Society of Thoracic Surgeons-European Respiratory Society Collaborative Course on Thoracic Oncology (February 2023). Original lectures and talks and their relevant references were included. An additional literature search was conducted and peer-reviewed studies in English (December 2022 to June 2023) from the PubMed/Medline databases were evaluated with regards to immediate affinity of the published papers to the original talks presented at the course. An updated literature search was conducted (June 2023 to December 2023) to ensure that updated literature is included within this article. RESULTS: Lung cancer screening suspicious findings are expected to increase the number of diagnostic investigations required therefore impacting on current capacity and resources. Healthcare systems already face a shortage of imaging and diagnostic slots and they are also challenged by the shortage of interventional radiologists. Thoracic surgery will be impacted by the wider lung cancer screening implementation with increased volume and earlier stages of lung cancer. Nonsuspicious findings reported at lung cancer screening will need attention and subsequent referrals where required to ensure participants are appropriately diagnosed and managed and that they are not lost within healthcare systems. CONCLUSIONS: Implementation of lung cancer screening requires appropriate mapping of existing resources and infrastructure to ensure a tailored restructuring strategy to ensure that healthcare systems can meet the new needs.

The Impact of Model Assumptions on Personalized Lung Cancer Screening Recommendations.

BACKGROUND: Recommendations regarding personalized lung cancer screening are being informed by natural-history modeling. Therefore, understanding how differences in model assumptions affect model-based personalized screening recommendations is essential. DESIGN: Five Cancer Intervention and Surveillance Modeling Network (CISNET) models were evaluated. Lung cancer incidence, mortality, and stage distributions were compared across 4 theoretical scenarios to assess model assumptions regarding 1) sojourn times, 2) stage-specific sensitivities, and 3) screening-induced lung cancer mortality reductions. Analyses were stratified by sex and smoking behavior. RESULTS: Most cancers had sojourn times <5 y (model range [MR]; lowest to highest value across models: 83.5%-98.7% of cancers). However, cancer aggressiveness still varied across models, as demonstrated by differences in proportions of cancers with sojourn times <2 y (MR: 42.5%-64.6%) and 2 to 4 y (MR: 28.8%-43.6%). Stage-specific sensitivity varied, particularly for stage I (MR: 31.3%-91.5%). Screening reduced stage IV incidence in most models for 1 y postscreening; increased sensitivity prolonged this period to 2 to 5 y. Screening-induced lung cancer mortality reductions among lung cancers detected at screening ranged widely (MR: 14.6%-48.9%), demonstrating variations in modeled treatment effectiveness of screen-detected cases. All models assumed longer sojourn times and greater screening-induced lung cancer mortality reductions for women. Models assuming differences in cancer epidemiology by smoking behaviors assumed shorter sojourn times and lower screening-induced lung cancer mortality reductions for heavy smokers. CONCLUSIONS: Model-based personalized screening recommendations are primarily driven by assumptions regarding sojourn times (favoring longer intervals for groups more likely to develop less aggressive cancers), sensitivity (higher sensitivities favoring longer intervals), and screening-induced mortality reductions (greater reductions favoring shorter intervals). IMPLICATIONS: Models suggest longer screening intervals may be feasible and benefits may be greater for women and light smokers. HIGHLIGHTS: Natural-history models are increasingly used to inform lung cancer screening, but causes for variations between models are difficult to assess.This is the first evaluation of these causes and their impact on personalized screening recommendations through easily interpretable metrics.Models vary regarding sojourn times, stage-specific sensitivities, and screening-induced lung cancer mortality reductions.Model outcomes were similar in predicting greater screening benefits for women and potentially light smokers. Longer screening intervals may be feasible for women and light smokers.